Patients with uncontrolled gout may maintain a therapeutic response at 6 months with treatment with methotrexate (MTX) and pegloticase vs pegloticase alone, according to study results published in the Journal of Rheumatology.
In the current multicenter open-label study (ClinicalTrials.gov Identifier: NCT03635957), researchers enrolled adult patients (18-65 years) with uncontrolled gout from 6 sites around the United States. Uncontrolled gout was defined as having a serum uric acid level (sUA) ≥6 mg/dL before treatment initiation. All patients received treatment with MTX and pegloticase. A 4-week run-in period preceded the maximum 52-week treatment period. Patients received 15 mg per week of oral MTX and 1 mg per day of oral folic acid during the run-in period. Intravenous pegloticase was initiated during the 52-week treatment period at a dose of 8 mg every 2 weeks. Patients underwent study visits every 2 weeks, during which blood and urine samples were collected. The primary outcome was percentage of pegloticase responders at month 6, defined as sustained normalization of sUA (<6 mg/dL) for at least 80% of the month. Adverse events were monitored throughout the trial.
A total of 14 patients completed the MTX run-in period and received at least 1 dose of pegloticase. All patients were men; mean age was 49.3±8.7 years. The majority of patients were White and had visible tophi at study enrollment. Mean baseline sUA value prior to first pegloticase infusion was 9.2±2.5 mg/dL. Overall, 11 patients (78.6%) were considered pegloticase responders at month 6. The percentage of responders at month 3 was also 78.6%. Among responders, mean sUA change from baseline was -9.0±2.8 mg/dL at both weeks 14 and 24. In the total cohort, mean number of joints affected by tophi at baseline was 6.4±7.9. This number decreased to 2.6±3.5 joints at the final assessment.
Ten patients experienced 1 or more adverse event during the MTX run-in period. The most common events were gout flare, nausea, and abdominal discomfort. During the pegloticase period, all patients experienced 1 or more adverse event. The most common adverse events during MTX plus pegloticase treatment were gout flare (n=12; 85.7%), diarrhea (n=3; 21.4%), and upper respiratory tract infection (n=3; 21.4%). No serious adverse events were observed. No new safety signals were identified for either MTX or pegloticase.
These results support the efficacy of treatment with MTX combined with pegloticase in patients with gout. Methotrexate appeared to increase the percentage of pegloticase responders, though small cohort size may have limited data generalizability.
“These results support the need for a randomized study of methotrexate or placebo with pegloticase to validate these open label findings,” the investigators concluded.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Botson JK, Tesser JRP, Bennett R, et al. Pegloticase in combination with methotrexate in patients with uncontrolled gout: a multicenter, open-label study (MIRROR). Published online September 15, 2020. J Rheumatol. doi:10.3899/jrheum.200460